Survival motor neuron 2 pre-mRNA 5' splice site of intron 7 (SMN2 pre-mRNA 5'ss intron 7)

The Survival motor neuron 2 (SMN2) pre-mRNA 5' splice site of intron 7 is a critical regulatory sequence involved in the alternative splicing of the SMN2 gene (Lefebvre et al., 1995, Cell). In Spinal Muscular Atrophy (SMA), the primary SMN1 gene is lost or mutated, and patients rely on the nearly identical SMN2 gene; however, a C-to-T transition in SMN2 exon 7 weakens this 5' splice site, leading to frequent exon 7 skipping and the production of a truncated, unstable protein (Lorson et al., 1999, PNAS). This specific RNA sequence serves as a therapeutic target for small molecule splicing modifiers such as Risdiplam and Branaplam (Ratni et al., 2018, J. Med. Chem.). These drugs act by binding to the SMN2 pre-mRNA at the exon 7-intron 7 junction, stabilizing the interaction with the U1 small nuclear ribonucleoprotein (snRNP) and promoting the inclusion of exon 7 (Campagne et al., 2019, Nat. Commun.). This mechanism increases the levels of full-length, functional SMN protein, thereby addressing the underlying cause of SMA and improving motor function in affected patients (Dhillon, 2020, Drugs).

Other names

SMN2 exon 7-intron 7 junctionSMN2 5'ssSMN2 intron 7 5' splice siteSMN2 pre-mRNA exon 7 5' splice site

Small molecule splicing modifier that binds to the 5' splice site of intron 7 and the U1 snRNP, stabilizing the complex to promote exon 7 inclusion in SMN2 mRNA (Ratni et al., 2018, J. Med. Chem.; Campagne et al., 2019, Nat. Commun.).